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Abstract

Splenic resident dendritic cell (DC) populations occupy sentinel positions for the capture and presentation of blood-borne antigens. Here we show that the chemotactic receptor EBI2 (GPR183) is differentially expressed on splenic DC subsets and regulates the positioning and homeostasis of DCs within the spleen. EBI2 and its ligand 7α, 25-OHC were required for the generation of the splenic CD4+ DC subset and the localization of DCs in bridging channels. Absence of EBI2 on DCs resulted in defects in both the activation of CD4+ T cells and the generation of antibody responses. Regulated expression of EBI2 on DC populations is therefore critical for the development and correct positioning of splenic DCs and the initiation of immune responses.